All-trans retinoic-acid inhibits heterodimeric bone morphogenetic protein 2/7-stimulated osteoclastogenesis, and resorption activity

• Published in: Cell & bioscience 2018-08, Vol.8 (1), p.48-48, Article 48
• Main Authors: Bi, Wenjuan, Liu, Yi, Guo, Jing, Lin, Zhen, Liu, Jinsong, Zhou, Miao, Wismeijer, Daniel, Pathak, Janak L, Wu, Gang
• Format: Article
• Language: English
• Subjects: Acids; All-trans retinoic acid; Bone cancer; Bone loss; Bone marrow; Bone morphogenetic protein 2; Bone morphogenetic proteins; Bone regeneration; Bone resorption; Cancer; Cancer therapies; Dosage and administration; Drug dosages; Gene expression; Genetic engineering; Health aspects; Heterodimeric bone morphogenetic protein 2/7; Inflammation; Kinases; Macrophages; Metastases; Metastasis; Nanoparticles; Osteoclast activity; Osteoclastogenesis; Osteoclasts; Osteogenesis; Osteoporosis; Physiology; Proteins; Retinoic acid receptors; Rheumatoid arthritis; TRANCE protein; Tretinoin
• ISSN: 2045-3701; 2045-3701
• DOI: 10.1186/s13578-018-0246-y

Bone regenerative heterodimeric bone morphogenetic protein 2/7 (BMP2/7) enhances but all-trans retinoic acid (ATRA) inhibits osteoclastogenesis. However, the effect of ATRA on physiological and/or BMP2/7-induced osteoclastogenesis in still unclear. In this study, we aimed to test the effect of combined treatment of BMP2/7 and ATRA on osteoclastogenesis, and resorption activity. All-trans retinoic acid (1 µM) ± BMP2/7 (5 or 50 ng/ml) was added in murine pre-osteoclasts cell line RAW264.7 or mouse bone marrow derived macrophages (BMM) cultures. Osteoclast marker gene expression, osteoclastogenesis, and resorption activity were analyzed. BMP2/7 robustly enhanced osteoclast maker gene expression, osteoclastogenesis, and resorption activity. Interestingly, ATRA completely inhibited osteoclast formation in presence or absence of BMP2/7. Pan-antagonist of retinoic acid receptors (RARs) and antagonist of RARα, β or γ failed to reverse the inhibitory effect of ATRA on osteoclastogenesis. ATRA strongly inhibited and expression. All-trans retinoic acid inhibits BMP2/7-induced osteoclastogenesis, and resorption activity possibly via RANKL-RANK pathway. Our findings from previous and current study suggest that combination of ATRA and BMP2/7 could be a novel approach to treat hyperactive osteoclast-induced bone loss such as in inflammation-induced severe osteoporosis and bone loss caused by cancer metastasis to bone.